7542-45-2

Synthetic route

(2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial (5056-17-7) + [(4E)-5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-pentadienyl]-triphenylphosphonium bromide → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions	Yield
Stage #1: (2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial; [(4E)-5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-pentadienyl]-triphenylphosphonium bromide With ethyloxirane In isopropyl alcohol for 18h; Heating / reflux; Stage #2: In dichloromethane Heating / reflux;	80%
In various solvent(s) at 63℃; for 20h; Condensation; Wittig reaction;	55%
With ethyloxirane at 63℃; for 20h;	54.7%

astaxanthin esters + tricaprilin (538-23-8) → astaxanthin octanoic acid monoester + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + di-O-octanoyl-all-trans-astaxanthin

Conditions	Yield
lipase PL (from Alcaligenes) In water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 4% B 79.3% C 1%
immobilized lipase In water at 45℃; for 96h; Product distribution / selectivity; Enzymatic reaction;	A 12.2% B 64% C 1%
immobilized lipase of Phenyl Toyopearl In water at 45℃; for 96h; Product distribution / selectivity; Enzymatic reaction;	A 14.1% B 61.6% C 2.8%

(2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial (5056-17-7) + [(4E)-5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-pentadienyl]-triphenylphosphonium bromide → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + semi-astacene (106776-90-3) + Triphenylphosphine oxide (791-28-6)

Conditions	Yield
Stage #1: (2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial; [(4E)-5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-3-methyl-2,4-pentadienyl]-triphenylphosphonium bromide With sodium methylate In methanol; dichloromethane at -5℃; for 19.6 - 20.5h; Stage #2: With acetic acid In methanol; dichloromethane Product distribution / selectivity;	A 75.8% B n/a C n/a

tricaprilin (538-23-8) + astaxanthin oleic acid diester → astaxanthin octanoic acid monoester + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + di-O-octanoyl-all-trans-astaxanthin

Conditions	Yield
lipase OF (from Candida) In water at 45℃; for 240h; Product distribution / selectivity; Enzymatic reaction;	A 27.2% B 72.8% C 1%

zeaxanthin (144-68-3) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions	Yield
With sodium bromate; sodium hydrogensulfite In chloroform at 20 - 30℃; for 3h;	72.14%
With sodium bromate; sodium hydrogensulfite In chloroform for 0.5h;	51%

Octanoic acid (124-07-2) + astaxanthin oleic acid diester → astaxanthin octanoic acid monoester + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + di-O-octanoyl-all-trans-astaxanthin

Conditions	Yield
lipase OF (from Candida) In water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 8.2% B 61.1% C 1%

astaxanthin esters + Octanoic acid (124-07-2) → astaxanthin octanoic acid monoester + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + di-O-octanoyl-all-trans-astaxanthin

Conditions	Yield
lipase OF (from Candida) In water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 10.5% B 42.6% C 1%
immobilized lipase In water at 45℃; for 96h; Product distribution / selectivity; Enzymatic reaction;	A 2% B 23.6% C 1%

astaxanthin esters + tricaprilin (538-23-8) → astaxanthin octanoic acid monoester + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions	Yield
immobilized lipase In hexane; water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 1% B 15.2%

astaxanthin cation radical → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions	Yield
With TX-100 In water Rate constant; Irradiation;

lycopene (502-65-8) + astaxanthin cation radical → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + lycopene radical cation

Conditions	Yield
In benzene Rate constant; pulse radiolysis;

zeaxanthin (144-68-3) + astaxanthin cation radical → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + zeaxanthin radical cation

Conditions	Yield
In benzene Rate constant; pulse radiolysis;

beta-carotene (7235-40-7) + astaxanthin cation radical → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + all-trans β-carotene radical cation

Conditions	Yield
In benzene Rate constant; pulse radiolysis;

astaxanthin dipalmitate (112421-21-3) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + astaxanthin palmitate (123159-02-4)

Conditions	Yield
With rainbow trout intestine lipolytic enzymes; water at 20℃; for 48h; pH=8.0; Product distribution; Further Variations:; Reagents;

astaxanthin decanoic acid diester → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + astaxanthin decanoic acid monoester

Conditions	Yield
With water; Candida rugosa lipase at 20℃; for 42h; pH=8.0; Product distribution; Further Variations:; Reagents;

(E)-Octadec-9-enoic acid 3,5,5-trimethyl-2-oxo-4-{(1E,3E,5E,7E,9E,11E,13E,15E,17E)-3,7,12,16-tetramethyl-18-[2,6,6-trimethyl-4-((E)-octadec-9-enoyloxy)-3-oxo-cyclohex-1-enyl]-octadeca-1,3,5,7,9,11,13,15,17-nonaenyl}-cyclohex-3-enyl ester → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + (E)-Octadec-9-enoic acid 4-[(1E,3E,5E,7E,9E,11E,13E,15E,17E)-18-(4-hydroxy-2,6,6-trimethyl-3-oxo-cyclohex-1-enyl)-3,7,12,16-tetramethyl-octadeca-1,3,5,7,9,11,13,15,17-nonaenyl]-3,5,5-trimethyl-2-oxo-cyclohex-3-enyl ester

Conditions	Yield
With water; Candida rugosa lipase at 20℃; for 42h; pH=8.0; Product distribution; Further Variations:; Reagents;

astaxanthin dieicosapentaenoate → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + astaxanthin eicosapentaenoate

Conditions	Yield
With rainbow trout intestine lipolytic enzymes; water at 20℃; for 48h; pH=8.0; Product distribution; Further Variations:; Reagents;

astaxanthin didocosahexaenoate → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + astaxanthin docosahexaenoate

Conditions	Yield
With rainbow trout intestine lipolytic enzymes; water at 20℃; for 48h; pH=8.0; Product distribution; Further Variations:; Reagents;

6-Methyl-hept-5-en-2-on (110-93-0) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 14 steps 1.1: NaH / tetrahydrofuran / 0 - 20 °C 1.2: 89.4 percent / tetrahydrofuran / 2 h / 20 °C 2.1: 86 percent / conc. H2SO4 / nitromethane / 0.5 h / 0 °C 3.1: 95 percent / m-chloroperbenzoic acid / ethyl acetate / 0 - 20 °C 4.1: 96.5 percent / LDA / tetrahydrofuran / -40 - 20 °C 5.1: 66 percent / pyridinium chlorochromate / CH2Cl2 / 0 - 20 °C 6.1: p-toluenesulfonic acid; trimethyl orthoformate 6.2: 89 percent / HCl / acetone 7.1: 72 percent / DIBAL-H / petroleum ether / 1 h / -60 - 20 °C 8.1: nBuLi / tetrahydrofuran / -20 °C 8.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 9.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 10.1: 97 percent / HCl / acetone; H2O 11.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 11.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 12.1: HBr / CH2Cl2 / 0 °C 13.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 14.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

geranonitrile (5146-66-7) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 13 steps 1.1: 86 percent / conc. H2SO4 / nitromethane / 0.5 h / 0 °C 2.1: 95 percent / m-chloroperbenzoic acid / ethyl acetate / 0 - 20 °C 3.1: 96.5 percent / LDA / tetrahydrofuran / -40 - 20 °C 4.1: 66 percent / pyridinium chlorochromate / CH2Cl2 / 0 - 20 °C 5.1: p-toluenesulfonic acid; trimethyl orthoformate 5.2: 89 percent / HCl / acetone 6.1: 72 percent / DIBAL-H / petroleum ether / 1 h / -60 - 20 °C 7.1: nBuLi / tetrahydrofuran / -20 °C 7.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 8.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 9.1: 97 percent / HCl / acetone; H2O 10.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 10.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 11.1: HBr / CH2Cl2 / 0 °C 12.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 13.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

5-methyl-4-hexenenitrile (23089-87-4) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 15 steps 1.1: 70 percent / diethyl ether / 1 h / 0 °C 2.1: NaH / tetrahydrofuran / 0 - 20 °C 2.2: 89.4 percent / tetrahydrofuran / 2 h / 20 °C 3.1: 86 percent / conc. H2SO4 / nitromethane / 0.5 h / 0 °C 4.1: 95 percent / m-chloroperbenzoic acid / ethyl acetate / 0 - 20 °C 5.1: 96.5 percent / LDA / tetrahydrofuran / -40 - 20 °C 6.1: 66 percent / pyridinium chlorochromate / CH2Cl2 / 0 - 20 °C 7.1: p-toluenesulfonic acid; trimethyl orthoformate 7.2: 89 percent / HCl / acetone 8.1: 72 percent / DIBAL-H / petroleum ether / 1 h / -60 - 20 °C 9.1: nBuLi / tetrahydrofuran / -20 °C 9.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 10.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 11.1: 97 percent / HCl / acetone; H2O 12.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 12.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 13.1: HBr / CH2Cl2 / 0 °C 14.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 15.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

2,6,6-trimethyl-2-cyclohexenecarbonitrile (57524-13-7) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 12 steps 1.1: 95 percent / m-chloroperbenzoic acid / ethyl acetate / 0 - 20 °C 2.1: 96.5 percent / LDA / tetrahydrofuran / -40 - 20 °C 3.1: 66 percent / pyridinium chlorochromate / CH2Cl2 / 0 - 20 °C 4.1: p-toluenesulfonic acid; trimethyl orthoformate 4.2: 89 percent / HCl / acetone 5.1: 72 percent / DIBAL-H / petroleum ether / 1 h / -60 - 20 °C 6.1: nBuLi / tetrahydrofuran / -20 °C 6.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 7.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 8.1: 97 percent / HCl / acetone; H2O 9.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 9.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 10.1: HBr / CH2Cl2 / 0 °C 11.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 12.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

(2E,4E)-3-methyl-5-(2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-2,4-pentadienol (29538-78-1) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 1.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 2.1: HBr / CH2Cl2 / 0 °C 3.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 4.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

2,4,4-Trimethylcyclohex-2-en-1-one-3-carbonitrile (56830-39-8) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: p-toluenesulfonic acid; trimethyl orthoformate 1.2: 89 percent / HCl / acetone 2.1: 72 percent / DIBAL-H / petroleum ether / 1 h / -60 - 20 °C 3.1: nBuLi / tetrahydrofuran / -20 °C 3.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 4.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 5.1: 97 percent / HCl / acetone; H2O 6.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 6.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 7.1: HBr / CH2Cl2 / 0 °C 8.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 9.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

3-hydroxy-2,6,6-trimethyl-2-cyclohexenecarbonitrile (145106-79-2) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 10 steps 1.1: 66 percent / pyridinium chlorochromate / CH2Cl2 / 0 - 20 °C 2.1: p-toluenesulfonic acid; trimethyl orthoformate 2.2: 89 percent / HCl / acetone 3.1: 72 percent / DIBAL-H / petroleum ether / 1 h / -60 - 20 °C 4.1: nBuLi / tetrahydrofuran / -20 °C 4.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 5.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 6.1: 97 percent / HCl / acetone; H2O 7.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 7.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 8.1: HBr / CH2Cl2 / 0 °C 9.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 10.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

(2E,4E)-3-methyl-5-(4-hydroxy-2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-2,4-pentadienol (94669-81-5) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: HBr / CH2Cl2 / 0 °C 2: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 3: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

2,3-epoxy-2,6,6-trimethyl-1-cyclohexanecarbonitrile (264279-20-1) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: 96.5 percent / LDA / tetrahydrofuran / -40 - 20 °C 2.1: 66 percent / pyridinium chlorochromate / CH2Cl2 / 0 - 20 °C 3.1: p-toluenesulfonic acid; trimethyl orthoformate 3.2: 89 percent / HCl / acetone 4.1: 72 percent / DIBAL-H / petroleum ether / 1 h / -60 - 20 °C 5.1: nBuLi / tetrahydrofuran / -20 °C 5.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 6.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 7.1: 97 percent / HCl / acetone; H2O 8.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 8.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 9.1: HBr / CH2Cl2 / 0 °C 10.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 11.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

2,10,10-trimethyl-4,7-dioxaspiro[4,5]dec-1-enecarbaldehyde (264279-23-4) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 7 steps 1.1: nBuLi / tetrahydrofuran / -20 °C 1.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 2.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 3.1: 97 percent / HCl / acetone; H2O 4.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 4.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 5.1: HBr / CH2Cl2 / 0 °C 6.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 7.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

2,10,10-trimethyl-4,7-oxadispiro[4,5]dec-1-enecarbonitrile (264279-22-3) → 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: 72 percent / DIBAL-H / petroleum ether / 1 h / -60 - 20 °C 2.1: nBuLi / tetrahydrofuran / -20 °C 2.2: 79 percent / tetrahydrofuran / 1 h / 0 - 20 °C 3.1: 52 percent / DIBAL-H / petroleum ether / -80 - -20 °C 4.1: 97 percent / HCl / acetone; H2O 5.1: LDA / tetrahydrofuran / 0.17 h / -20 °C 5.2: 69 percent / (+)-(8,8-dichlorocamphorsulfonyl)oxaziridine / tetrahydrofuran / 1.25 h / -20 - 20 °C 6.1: HBr / CH2Cl2 / 0 °C 7.1: 1,2-epoxybutane / ethyl acetate / 24 h / 20 °C 8.1: 55 percent / various solvent(s) / 20 h / 63 °C View Scheme

succinic acid anhydride (108-30-5) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → rac-succinic acid mono-(4-{18-[4-(3-carboxy-propionyloxy)-2,6,6-trimethyl-3-oxo-cyclohex-1-enyl]-3,7,12,16-tetramethyl-octadeca-1,3,5,7,9,11,13,15,17-nonaenyl}-3,5,5-trimethyl-2-oxo-cyclohex-3-enyl) ester (769935-71-9)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 48h;	100%
With dmap In dichloromethane at 20℃; for 14h; Inert atmosphere; Darkness;
With dmap; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 48h;

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + N-tert-butoxycarbonyl-proline (15761-39-4) → BocProOH ester of astaxanthin

Conditions	Yield
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃;	100%

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + 2,6-bis-tert-butoxycarbonylamino-hexanoic acid (2483-46-7, 65360-27-2, 119962-72-0) → bocLys(boc)OH ester of astaxanthin

Conditions	Yield
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 18h;	100%

dimethyl phosphorobromidate (24167-74-6) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → bis-dimethylphosphate ester of astaxanthin

Conditions	Yield
With methyl imidazole In dichloromethane at 37℃; for 144h;	100%

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + C16H30N2O6 → C52H76N4O6*4H(1+)

Conditions	Yield
With dmap; diisopropyl-carbodiimide In dichloromethane for 18h; Darkness; Inert atmosphere;	100%

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → 3,3'-dichlorocanthaxanthin

Conditions	Yield
With 1-chloro-1-(dimethylamino)-2-methyl-1-propene In dichloromethane at 20℃;	95%
Multi-step reaction with 2 steps 1: pyridine / CH2Cl2 / 0 °C 2: n-Bu4NCl / tetrahydrofuran View Scheme

all cis-5,8,11,14,17-eicosapentaenoic acid (10417-94-4) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → astaxanthin dieicosapentaenoate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	92%

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + 1-hexadecylcarboxylic acid (57-10-3) → astaxanthin dipalmitate (112421-21-3)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	92%

docosahexaenoic acid (6217-54-5) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → astaxanthin didocosahexaenoate

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 24h;	91%

Octanoic acid (124-07-2) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → di-O-octanoyl-all-trans-astaxanthin

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 19h;	90%

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + 4-(dimethylamino)butyric acid hydrochloride (69954-66-1) → (dimethylamino)butyric acid diester of astaxanthin

Conditions	Yield
With dmap; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 36h;	77.7%

HOBT-H2O + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + 4-(dimethylamino)butyric acid hydrochloride (69954-66-1) → (dimethylamino)butyric acid diester of astaxanthin + (dimethylamino)butyric acid diester (LVIII)

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; N,N-dimethyl-formamide	A n/a B 77.7%
With dmap; N-ethyl-N,N-diisopropylamine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; N,N-dimethyl-formamide	A n/a B 77.7%
With dmap; N-ethyl-N,N-diisopropylamine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; N,N-dimethyl-formamide	A n/a B 77.7%

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + acetyl chloride (75-36-5) → 3-acetoxy-3'-hydroxycanthaxanthin

Conditions	Yield
With pyridine In dichloromethane at 0℃;	64%

4-morpholinocarbonyl chloride (15159-40-7) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → astaxanthin 4-morpholine monocarbamate + astaxanthin 4-morpholine dicarbamate

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 36h;	A 33.17% B 33.42%

Octanoic acid (124-07-2) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → astaxanthin octanoic acid monoester + di-O-octanoyl-all-trans-astaxanthin

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 18h;	A 32% B 22%
lipase OF (from Candida) In water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 6% B 1%
immobilized lipase In water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 4.2% B 1%

cis-aconitic anhydride (6318-55-4) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → astaxanthin aconitic monoester + astaxanthin aconitic diester

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 36h;	A 13.25% B 27.67%

2-Methoxypropene (116-11-0) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → (3RS,3'RS)-Astaxanthin-bis(1-methoxy-1-methylaethyl)aether

Conditions	Yield
With toluene-4-sulfonic acid at 0℃; for 0.25h;	27%

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + citric acid (77-92-9) → astaxanthin citric acid monoester + astaxanthin citric acid diester

Conditions	Yield
With dmap; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In dichloromethane at 20℃; for 36h;	A 26.56% B 7.81%

3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) + 4-(dimethylamino)butyric acid hydrochloride (69954-66-1) → dimethylaminobutyric acid monoester of astaxanthin

Conditions	Yield
With dmap; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 36h;	24.5%
With dmap; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 36h;	24.5%

tricaprilin (538-23-8) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → astaxanthin octanoic acid monoester + di-O-octanoyl-all-trans-astaxanthin

Conditions	Yield
immobilized lipase In hexane; water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 23.9% B 2.3%
immobilized lipase In water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 21.9% B 2.6%
HPA25 resin-immobilized lipase In water at 45℃; for 72h; Product distribution / selectivity; Enzymatic reaction;	A 19.2% B 1%

glutathion (70-18-8) + 3,3'-dihydroxy-β,β-carotene-4,4'-dione (7542-45-2) → glutathione monoester of astaxanthin

Conditions	Yield
With dmap; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In DMF (N,N-dimethyl-formamide); dichloromethane at 20℃; for 36h;	23.61%

Upstream product

• 5056-17-7 (2E,4E,6E)-2,7-dimethyl-2,4,6-octatrienedial 
• 502-65-8 lycopene 
• 144-68-3 zeaxanthin 
• 7235-40-7 beta-carotene 
• 112421-21-3 astaxanthin dipalmitate 
• 110-93-0 6-Methyl-hept-5-en-2-on 
• 5146-66-7 geranonitrile 
• 23089-87-4 5-methyl-4-hexenenitrile 
• 57524-13-7 2,6,6-trimethyl-2-cyclohexenecarbonitrile 
• 29538-78-1 (2E,4E)-3-methyl-5-(2,6,6-trimethyl-3-oxo-1-cyclohexen-1-yl)-2,4-pentadienol 
• 56830-39-8 2,4,4-Trimethylcyclohex-2-en-1-one-3-carbonitrile 
• 145106-79-2 3-hydroxy-2,6,6-trimethylcyclohex-1-enecarbonitrile 
• 94669-81-5 (E)-6-Hydroxy-3-(5-hydroxy-3-methyl-1,3-pentadienyl)-2,4,4-trimethyl-2-cyclohexen-1-on 
• 264279-20-1 2,3-epoxy-2,6,6-trimethyl-1-cyclohexanecarbonitrile 

Downstream Products

• 76832-21-8 all-trans-astaxanthin diacetate 
• 123159-02-4 astaxanthin palmitate 
• 112421-21-3 astaxanthin dipalmitate 

Relevant academic research and scientific papers

METHOD FOR THE PREPARATION OF OXYCAROTENOIDS

A high-yield process for preparing astaxanthin (3,3'-dihydroxy-β, β- carotene-4, 4'- dione) from silylated derivatives of zeaxanthin (3,3'-dihydroxy-β, β- carotene-3, 3'-diol), whether it be of synthetic or natural origin, is described.

Method for Improving Flavor of Astaxanthin-Containing Extract

A method for improving the flavor of an astaxanthin-containing extract of the present invention includes the steps of: mixing 0.5 to 1000 parts by weight of ethanol and 1 part by weight of the astaxanthin-containing extract so as to obtain an ethanol mixture; collecting a solid precipitated from the ethanol mixture obtained; and drying the solid collected. In particular, the astaxanthin-containing extract, i.e., the starting material, is an extract from a green alga.

CRYSTAL FORMS OF ASTAXANTHIN

This invention describes previously undisclosed mixtures of specific crystal forms of astaxanthin and the individual crystal forms designated crystal Form I and II together with methods for preparing said crystal Forms. Methods for preparing nutritional dosage forms comprising said novel astaxanthin crystal forms for the life science industry are also disclosed.

PROCESS FOR THE SYNTHESIS OF INTERMEDIATES FOR THE PREPARATION OF ASTAXANTHIN

The present invention relates to a process for the preparation of intermediates useful in the synthesis of Astaxanthin, in particular C15-Wittig salts, but also 4-oxo-β-ionones, 3-hydroxy-4-oxo-β-ionones and the aryl esters thereof. 4-oxo-β-ionone is prepared by starting from a β-ionone by oxidation with bromates in the presence of iodine or iodide. 3-hydroxy-4-oxo-β-ionone is prepared in 4 steps, starting from 4 -oxo- β-ionone by oxidation with peracids; the aryl esters thereof are solids that are easily isolated and purified by crystallisation, and may be converted in 5 steps to C15-Wittig salts and finally, by the Wittig reaction, to Astaxanthin.

PROCESS FOR THE PREPARATION OF ASTAXANTHIN

The invention therefore relates to a process for the preparation of astaxanthin of the formula I by reacting 2 mol of the triphenylphosphonium salt of the general formula II in which X represents chlorine, bromine or the (HSO4) radical, preferably bromine, in a Wittig reaction with one mol of the C10-dialdehyde of the formula III which is characterized in that a) the starting compounds of the formulae II and III are taken up in a solvent, the mixture is cooled to a temperature of not more than 10°C, preferably -18°C to +5°C, b) about 0.9 to 1.5, preferably 0.9 to 1.2, mol of a base per mole of triphenylphosphonium salt are added to the resulting reaction mixture at a temperature of not more than 10°C, preferably -18°C to +5°C, c) the base is metered and mixed in over a predetermined reaction time T so that at least a ? base equivalent is added to the reaction mixture continuously or quasicontinuously within a timespan T' ?T and the remainder of the base within the remaining reaction time.

RECOVERY OF COMPOUNDS USING A NATURAL ADSORBENT

The invention provides a method for recovery of compounds by adsorption fish scales. The method can be used for natural and synthetic compounds such as various natural pigments including astaxanthin in an esterified or not and synthetic astaxanthin in free form, or other carotenoid compounds. Fish scales with an adsorbed compound may be used as a source of the compound both for human and animal consumption. In particular, fish scales with adsorbed astaxanthin provide a calcium-rich nutritional supplement with beneficial anti-oxidant properties.

Carotenoid ether analogs or derivatives for the inhibition and amelioration of disease

A method for inhibiting and/or ameliorating the occurrence of diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals in a subject whereby a subject is administered a carotenoid analog or derivative, either alone or in combination with another carotenoid analog or derivative, or co-antioxidant formulation. The analog or derivative is administered such that the subject's risk of experiencing diseases associated with reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals may be thereby reduced. The analog or analog combination may be administered to a subject for the inhibition and/or amelioration of any disease that involves production of reactive oxygen species, reactive nitrogen species, radicals and/or non-radicals. In some embodiments, the invention may include a chemical compound including an at least partially water soluble carotenoid analog or derivative. The carotenoid analog may include a conjugated polyene with between 7 to 14 double bonds. The conjugated polyene may include a cyclic ring including at least one substituent. In some embodiments, a cyclic ring of a carotenoid analog or derivative may include at least one substituent. The substituent may be coupled to the cyclic ring with an ether functionality.

ASTAXANTHIN MEDIUM-CHAIN FATTY ACID ESTER, PROCESS FOR PRODUCING THE SAME AND COMPOSITION CONTAINING THE ESTER

The present invention provides an astaxanthin medium-chain fatty acid ester, which is expected to be applied in the fields of food, cosmetics and pharmaceuticals, and has higher digestibility and tissue penetration than long chain fatty acid ester form astaxanthins. When the synthesis of an astaxanthin medium-chain fatty acid ester is attempted using the catalytic action of lipase by conventional methods, ester cannot be formed. However, according to the present invention, a composition comprising an astaxanthin medium-chain fatty acid monoester and/or diester is produced by adding a certain amount of water into a reaction system and reacting an astaxanthin or a long chain fatty acid ester thereof with a medium-chain fatty acid, a triglyceride thereof or a suitable ester. Moreover, these monoesters and/or diesters are isolated, as necessary. The present invention further provides food or cosmetics comprising the composition of the present invention.

Fatty acid selectivity of microbial lipase and lipolytic enzymes from salmonid fish intestines toward astaxanthin diesters

The objective of the work described in this paper was to study a possible FA selectivity of digestive lipolytic enzymes isolated from salmon and trout intestines toward astaxanthin diesters of various FA composition and compare it with the FA selectivity of microbial lipase. Astaxanthin diesters of varying FA composition were prepared in excellent yields (>90%) by chemical esterification using a carbodiimide coupling agent. The astaxanthin diesters were screened in a hydrolysis reaction by various commercially available lipases. The highest conversion rates were observed with the Candida rugosa lipase, which discriminated against n-3 PUFA. The rate of hydrolysis was determined by HPLC. Digestive lipolytic enzymes isolated from salmon and rainbow trout intestines displayed reversed FA selectivity. Thus, astaxanthin diesters highly enriched with n-3 PUFA including EPA and DHA were observed to be hydrolyzed at a considerably higher rate than the more saturated esters. Similar trends in FA selectivity were observed in the hydrolysis of fish oil TAG by the digestive lipolytic enzyme mixtures.

Preparation of astaxanthin

The present invention provides a method for preparing astaxanthin from zeaxanthin. Specifically, the present invention provides a method for said conversion using a halogenating agent with the salt of chloric or bromic acid in an inert solvent.